全文获取类型
收费全文 | 70886篇 |
免费 | 5261篇 |
国内免费 | 2482篇 |
出版年
2023年 | 1139篇 |
2022年 | 1060篇 |
2021年 | 2214篇 |
2020年 | 2348篇 |
2019年 | 3262篇 |
2018年 | 2835篇 |
2017年 | 2022篇 |
2016年 | 2010篇 |
2015年 | 2513篇 |
2014年 | 4741篇 |
2013年 | 5893篇 |
2012年 | 3653篇 |
2011年 | 4691篇 |
2010年 | 3572篇 |
2009年 | 3868篇 |
2008年 | 3940篇 |
2007年 | 3967篇 |
2006年 | 3518篇 |
2005年 | 3053篇 |
2004年 | 2703篇 |
2003年 | 2146篇 |
2002年 | 1927篇 |
2001年 | 1223篇 |
2000年 | 937篇 |
1999年 | 918篇 |
1998年 | 855篇 |
1997年 | 638篇 |
1996年 | 586篇 |
1995年 | 612篇 |
1994年 | 565篇 |
1993年 | 431篇 |
1992年 | 431篇 |
1991年 | 356篇 |
1990年 | 293篇 |
1989年 | 241篇 |
1988年 | 211篇 |
1987年 | 184篇 |
1986年 | 161篇 |
1985年 | 272篇 |
1984年 | 455篇 |
1983年 | 334篇 |
1982年 | 347篇 |
1981年 | 264篇 |
1980年 | 201篇 |
1979年 | 194篇 |
1978年 | 172篇 |
1977年 | 143篇 |
1976年 | 115篇 |
1975年 | 108篇 |
1973年 | 104篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Liyi Xu Jiamin Chen Litao Jia Xiao Chen Faycal Awaleh Moumin Jianting Cai 《Journal of cellular and molecular medicine》2020,24(24):14392
Gastric cancer is a major cause of mortality worldwide. The glutamate/aspartate transporter SLC1A3 has been implicated in tumour metabolism and progression, but the roles of SLC1A3 in gastric cancer remain unclear. We used bioinformatics approaches to analyse the expression of SLC1A3 and its role in gastric cancer. The expression levels of SLC1A3 were examined using RT‐qPCR and Western bolting. SLC1A3 overexpressing and knock‐down cell lines were constructed, and the cell viability was evaluated. Glucose consumption, lactate excretion and ATP levels were determined. The roles of SLC1A3 in tumour growth were evaluated using a xenograft tumour growth model. SLC1A3 was found to be overexpressed in gastric cancer, and this overexpression was associated with poor prognosis. In vitro and in vivo assays showed that SLC1A3 affected glucose metabolism and promoted gastric cancer growth. GSEA analysis suggested that SLC1A3 was positively associated with the up‐regulation of the PI3K/AKT pathway. SLC1A3 overexpression activated the PI3K/AKT pathway and up‐regulated GLUT1, HK II and LDHA expression. The PI3K/AKT inhibitor LY294002 prevented SLC1A3‐induced glucose metabolism and cell proliferation. Our findings indicate that SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway. SLC1A3 is therefore a potential therapeutic target in gastric cancer. 相似文献
92.
Lizhi Lin Jialiang Wen Bangyi Lin Adheesh Bhandari Danni Zheng Lingguo Kong Yinghao Wang Ouchen Wang Yizuo Chen 《Journal of cellular and molecular medicine》2020,24(23):14059
The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up‐regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf‐like PTC patients with higher IMUP expression had shorter disease‐free survival. The biological function of IMUP in PTC cell lines (KTC‐1 and TPC‐1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis‐related molecules were identified by real‐time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down‐regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC. 相似文献
93.
Ronald T. Riley Douglas E. Goeger William P. Norred Richard J. Cole Joe W. Dorner 《Journal of biochemical and molecular toxicology》1987,2(3):251-264
In a previous study (1) we demonstrated that increased tetraphenylphosphonium (TPP) uptake by renal epithelial cells (LLC-PK1) exposed to the fungal metabolite cyclopiazonic acid (CPA) was not a result of hyperpolarization across the plasma membrane even though CPA-potentiated TPP uptake could be totally inhibited by the depolarizing agent carbonylcyanide-m-chlorophenylhydrazone (CCCP). We now demonstrate that CPA potentiates TPP accumulation by proliferating skeletal muscle (L6) and LLC-PK1 cells but not by nonproliferating primary rat hepatocytes. In LLC-PK1 cells, CPA-potentiated TPP accumulation is observed in cells at all ages. In s cells, CPA-potentiated TPP accumulation is maximal soon after subculturing, and as the cells age they become less sensitive to CPA until TPP accumulation by CPA-treated cells approaches that of untreated cells. The temporal change in sensitivity of L6 cells to CPA may be related to biochemical and/or metabolic changes which occur as the cells age in culture. Hepatocytes, LLC-PK1 cells, and L6 cells permeabilized by freeze-thaw lysis, all exhibit CPA-potentiated TPP partitioning, even in the presence of CCCP. This result indicates that both TPP and CPA must have access to the intracellular space in order for potentiated TPP partitioning to be observed. We hypothesize that the site of interaction between CPA and TPP is intracellular and probably associated with the cytoplasmic side of the plasma membrane and possibly the mitochondria. 相似文献
94.
Karl E. Andersson George S. Drummond Umberto Freddara Mohinder K. Sardana Shigeru Sassa 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,676(3):289-299
The effects of single large doses of the porphyrin-heme precursor ?d-aminolevulinic acid on tissue porphyrins and on δ-aminolevulinate synthase and heme oxygenase, the rate-living enzymes of liver heme synthesis and degradation respectively, were studied in the chick embryo in ovo, in the mouse and in the rat. δ-Aminolevulinic acid treatment produced a distinctive pattern characterized by extensive tissue porphyrin accumulation and alterations in these rate-limiting enzymes in the liver. Repression of basal or allylisopropylacetamide-induced liver δ-aminolevulinate synthase was observed and, in the mouse and the rat, induction of liver heme oxygenase after δ-aminolevulinic acid treatment, in a manner similar to the known effects of hemin on these enzymes. In the chick embryo liver in ovo heme oxygenase was substantially higher than in rat and mouse liver, and was not significantly induced by δ-aminolevulinic acid or other compounds, including hemin, CS2 and CoCl2. Levulinic acid, an analogue of δ-aminolevulinic acid, did not induce heme oxygenase in mouse liver. δ-Aminolevunilic acid treatment did not impair ferrochelatase activity but was associated with slight and variable decreases in liver cytochrome P-450. Treatment of chick embryos with a small ‘priming’ dose of 1,4-dihydro-3,5-dicarbethoxycollidine, which impairs liver ferrochelatase activity, accentuated porphyrin accumulation after δ-aminolevulinic acid in the liver. These observations indicate that exogenous δ-aminolevulinic acid is metabolized to porphyrins in a number of tissues and, at least in the liver, to a physiologically significant amount of heme, thereby producing an increase in the size of one or more of the heme pools that regulate both heme systhesis and degradation. It is also possible than when δ-aminolevulinic acid is markedly overproduced in vivo it may be transported to many tissues and re-enter the heme pathway and alter porphyrin-heme metabolism in cells and tissues other than those in which its overproduction primarily occurs. 相似文献
95.
96.
97.
When Ehrlich ascites tumour cells are induced to proliferate by serum stimulation, the ornithine decarboxylase (ODC) activity increases rapidly and reaches two to three peaks during the first 24 h. Inhibition of the first peak in ODC activity (occurring at 4 h) by adding alpha-difluoromethylornithine (DFMO) within 2 h of serum stimulation, results in maximal growth inhibition. Under these conditions, similar degrees of polyamine depletion are achieved. When DFMO is added 3 h after seeding, however, enough polyamines have already accumulated during the initial burst in ODC activity to reduce the antiproliferative effect of the drug. The antiproliferative effect is further reduced when DFMO is added 6 h after seeding. When DFMO is added 23 h after seeding, i.e. after maximal accumulation of polyamines, there is no inhibition of cell proliferation. These findings are important to consider both when designing experimental as well as clinical regimens for this drug. 相似文献
98.
AMPA receptors mediate fast excitatory synaptic transmission in the brain, and are dynamically regulated by phosphorylation of multiple residues within the C-terminal domain. CaMKII phosphorylates Ser831 within the AMPA receptor GluA1 subunit to increase single channel conductance, and biochemical studies show that PKC can also phosphorylate this residue. In light of the discovery of additional PKC phosphorylation sites within the GluA1 C-terminus, it remains unclear whether PKC phosphorylation of Ser831 increases GluA1 conductance in intact receptors. Here, we report that the purified, catalytic subunit of PKC significantly increases the conductance of wild-type GluA1 AMPA receptors expressed in the presence of stargazin in HEK293T cells. Furthermore, the mutation GluA1-S831A blocks the functional effect of PKC. These findings suggest that GluA1 AMPA receptor conductance can be increased by activated CaMKII or PKC, and that phosphorylation at this site provides a mechanism for channel modulation via a variety of protein signaling cascades. 相似文献
99.
Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress
The p63 gene product regulates epithelial morphogenesis and female germline integrity. In this study, we show that cyclin‐dependent kinase 5 and Abl enzyme substrate 1 (Cables1) interacts with the trans‐activating (TA) p63α isoform to protect it from proteasomal degradation. Using the female germline of Cables1‐null mice as an in vivo model, we demonstrate further that oocytes lacking Cables1 exhibit lower basal levels of TAp63α and reduced accumulation of phosphorylated TAp63α in response to genotoxic stress. This in turn enhances the survival of these cells after ionizing radiation exposure. Thus, Cables1 modulates p63 protein stability and function during genotoxic stress. 相似文献
100.
Abstract. Plant cover was visually estimated by five observers, independent of each other, in a species‐rich grassland in the Bílé Karpaty Mts., southeastern Czech Republic, in seven plots ranging from 0.001 to 4 m2. Variation of total plant cover among the observers was high at small scales: 0.001–0.016 m2; coefficient of variation, CV = 35 to 45%, but much lower at larger scales: 0.06–4 m2; CV = 7 to 15%. Differences between visual estimates of plant cover of individual species made by different observers were affected by plot size, total cover and morphology of particular plants. CV of the cover of individual species ranged from 0 to 225% and decreased with increasing plot size. For abundant plants the CV attained ca. 50%, independent of plot size. In spite of a very high number of sterile plants with similar leaf morphology and colour, the observed variation in cover estimates in the studied grassland was comparable with results reported from other vegetation types. Differences between estimates by individual observers were often larger than usual year to year changes in undisturbed grasslands. Therefore, I suggest that to avoid difficulties in the interpretation of results based on plant cover data obtained from visual estimates, several observers should always work together, adjusting their extreme estimates. 相似文献